In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-04-29)
Abstract:
Multiple glycosyltransferases are essential for the proper modification of alpha-dystroglycan, as mutations in the encoding genes cause congenital/limb-girdle muscular dystrophies. Here we elucidate further the structure of an O -mannose-initiated glycan on alpha-dystroglycan that is required to generate its extracellular matrix-binding polysaccharide. This functional glycan contains a novel ribitol structure that links a phosphotrisaccharide to xylose. ISPD is a CDP-ribitol (ribose) pyrophosphorylase that generates the reduced sugar nucleotide for the insertion of ribitol in a phosphodiester linkage to the glycoprotein. TMEM5 is a UDP-xylosyl transferase that elaborates the structure. We demonstrate in a zebrafish model as well as in a human patient that defects in TMEM5 result in muscular dystrophy in combination with abnormal brain development. Thus, we propose a novel structure—a ribitol in a phosphodiester linkage—for the moiety on which TMEM5, B4GAT1, and LARGE act to generate the functional receptor for ECM proteins having LG domains.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.14473.001
DOI:
10.7554/eLife.14473.002
DOI:
10.7554/eLife.14473.003
DOI:
10.7554/eLife.14473.004
DOI:
10.7554/eLife.14473.005
DOI:
10.7554/eLife.14473.006
DOI:
10.7554/eLife.14473.007
DOI:
10.7554/eLife.14473.008
DOI:
10.7554/eLife.14473.009
DOI:
10.7554/eLife.14473.010
DOI:
10.7554/eLife.14473.011
DOI:
10.7554/eLife.14473.012
DOI:
10.7554/eLife.14473.013
DOI:
10.7554/eLife.14473.014
DOI:
10.7554/eLife.14473.015
DOI:
10.7554/eLife.14473.016
DOI:
10.7554/eLife.14473.017
DOI:
10.7554/eLife.14473.018
DOI:
10.7554/eLife.14473.019
DOI:
10.7554/eLife.14473.020
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3